Prospective observational study of drug utilization in neonatal seizure at a tertiary care hospital with Pharmacoeconomics

Ketan A. Patil, Santoshkumar R. Jeevangi, Sharanabasappa .


Background: Seizures are the most common indicator of significant neurologic dysfunction in neonatal period with incidence of 11.7/1000 live births. Phenobarbitone is used as first line of treatment since 1900s. Newer anti-epileptic drugs (AED) available are Levetiracetam, Topiramate etc. Present study focused on utilization pattern of AED, treatment outcomes and to study economic burden of disease.

Methods: An observational study was done on 100 neonates admitted to Neonatal Intensive Care Unit in Basaveshwara hospital, Kalaburagi (June 2016-May 2017). Prescription data was entered into specially designed proforma, WHO core indicators were determined. The data was analyzed using descriptive statistics and presented as means and percentages.

Results: Majority of neonates were male (58%) and 63% were diagnosed with subtle seizure. Out of 458 drugs prescribed, 201 were antiepileptics. 41% cases were successfully managed by monotherapy. Most commonly used drug was phenobarbitone (82%) and phenytoin (31%). Leviteracetam, newer AED was used in 3 refractory cases. The major combination of drugs used was Phenobarbitone-Phenytoin (24%). AED were rationally prescribed, but antibiotic was over-utilized(68%). 31% cases had adverse drug reaction. On average per prescription, number of drugs used were 4.6 and drug cost was Rs.3803/-. The total cost of illness per patient was Rs.16363/-.

Conclusions: AED utilization in neonatal seizures was in accordance to guidelines, with phenobarbitone being extensively used despite its potential neurotoxicity. The utilization of newer AED would increase if clinicians are supported with the safety and efficacy data. Although monotherapy was preferred with respect to AED, antibiotics were highly prescribed; hence awareness is needed to curb this practice.


Cost of illness, Drug utilization, Monotherapy, Neonatal seizures, Phenobarbitone

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McNamara JO. Pharmacotherapy of epilepsy. In: Brunton LL, Chabner BA, Knollman BC editors. Goodman & Gilman’s The Pharmacological Basis of Therapeutics, 12th edition. Newyork: McGraw-Hill;2011:583-608.

Ronen GM, Buckley D, Penney S, Streiner DL. Long-term prognosis in children with neonatal seizures: a population-based study. Neurol. 2007 Nov; 69(19):1816-1822.

Maggie Lo-Yee Yau, Eva Lai-Wah Fung, and Pak Cheung Ng. Response of levetiracetam in neonatal seizures. World J Clin Pediatr. 2015 Aug 8;4(3):45-9.

Helena Gama. Drug utilization studies. Med Files. 2008;22(2/3):69-74.

Rakhade SN, Jensen FE. Epileptogenesis in the immature brain: emerging mechanisms. Nat Rev Neurol. 2009;5(7):380-91.

Dzhala VI, Talos DM, Sdrulla DA, Brumback AC, Mathews GC, Benke TA, et al. NKCC1 transporter facilitates seizures in the developing brain. Nature Med. 2005 Nov;11(11):1205.

Mohamad A. Mikati and Abeer J. Hani: Neonatal Seizures In: Robert M. Kliegman, NELSON Textbook of Pediatrics; 20th edition, 2016; Elsevier;Canada:2849-2854.

Dulac O, Milh M, Holmes GL. Brain maturation and epilepsy. InHandbook of clinical neurology 2013 Jan 1;111:441-6. Elsevier.

Berg A, Jallon P, Preux P. The epidemiology of seizure disorders in infancy and childhood: definitions and classifications. In: O Dulac et al, eds, Handbook of Clinical Neurology. Pediatric Neurology, Part 1 3rd edition. Elsevier; Amsterdam, Netherlands; 2013:381-398.

Pressler RM1, Mangum B; Newly emerging therapies for neonatal seizures. Semin Fetal Neonatal Med. 2013 Aug;18(4):216-23.

Kumar A, Gupta A, Talukdar B. Clinico-etiological and EEG profile of neonatal seizures. Indian J Pediatr. 2007 Jan 1;74(1):33-7.

Lanska MJ, Lanska DJ, Baumann RJ, Kryscio RJ. A population-based study of neonatal seizures in Fayette County, Kentucky. Neurol. 1995 Apr 1;45(4):724-32.

Omene JA, Longe AC, Okolo AA. Seizures in the Nigerian neonate: Perinatal factors. Int J Gynecol Obstet. 1981 Aug;19(4):295-9.

Park W, Kim DY, Jung CZ, Kim SD. Clinical study of neonatal seizure. J Korean Child Neurol Soc. 1998 Oct 1;6(1):71-82.

Minchom P, Niswander K, Chalmers I, Dauncey M, Newcombe R, Elbourne D, et al. Antecedents and outcome of very early neonatal seizures in infants born at or after term. BJOG An Int J Obstet Gynaecol. 1987 May;94(5):431-9.

Saliba RM. Risk Factors for Neonatal Seizures: A Population-based Study, Harris County, Texas, 1992-1994. Am J Epidemiol. 2001 Jul 1;154(1):14-20.

Calciolari G, Perlman JM, Volpe JJ. Seizures in the Neonatal Intensive Care Unit of the 1980s: Types, Etiologies, Timing. Clin Pediatr (Phila). 1988 Mar 1;27(3):119-23.

Rodney A. Radtke. Pharmacokinetics of Levetiracetam. Epilepsia. 2001;42(Suppl 4):24-27.

Khan O, Chang E, Cipriani C, Wright C, Crisp E, Kirmani B. Use of intravenous levetiracetam for management of acute seizures in neonates. Pediatr Neurol. 2011Apr;44(4):265-9.

WHO. How to investigate drug use in health facilities: selected drug indicators, action program on essential drugs (DAP), Geneva, 1993:12-25. Available at:

Warrier I, Wei D, Natarajan G, Vali S, Aranda J. Patterns of drug utilization in a neonatal intensive care unit. J Clin Pharmacol. 2006 Apr;46(4):449-55.

Karande S, Sankhe P, Kulkarni M. Patterns of prescription and drug dispensing. Indian J Pediatr. 2005 Feb 1;72(2):117-21.